IL-6 is a cytokine that was discovered as a B-cell differentiation inducing factor and has a variety of bioactivities such as antibody production system, induction of biosynthesis of acute phase protein in the liver, and acceleration of proliferation of hematopoietic stem cells based on its synergistic effect with interleukin-3.
Accordingly, if the production of IL-6 can be regulated, the prevention and/or treatment of a disease considered to be associated with IL-6 can be realized.
As the disease considered to be associated with IL-6, for example, polyclonal B cell disorders (such as intra-atrial myxoma, Castleman syndrome, rheumatoid arthritis, cervical cancer, acquired immunodeficiency syndrome and alcoholic liver cirrhosis), lymphoid tumors (such as multiple myeloma and Lennert T lymphoma), mesangioproliferative nephritis, renal cell carcinoma, psoriasis and the like have been known (Bessatsu Igaku no Ayumi (Journal of Clinical and Experimental Medicine, Supplement) Cytokines, Kiso kara Rinsho Oyo made (from Basic to Clinical Research), 28-35 (1992)).
Recently, correlation between IL-6 and ocular inflammatory diseases such as age-related macular degeneration, diabetic retinopathy and diabetic macular edema has also become known (Invest. Ophthalmol. Vis. Sci. 47, E-Abstract 905 (2006), Diabetes. Res. Clin. Pract. 61, 93-101 (2003), Ophthalmology, 110, 1690-1696 (2003)).
Further, a lot of medicinal agents for regulating IL-6 have been known. For example, it is described in WO 2003/086371 that a benzimidazole derivative having an EP4 agonistic effect inhibits IL-6 production, and MRA which is an anti-IL-6 receptor antibody is described in STN Registry files CAS No. 375823-41-9.
On the other hand, a pyrrole derivative having a ureido group as a substituent is described along with the production examples in J. Chem. Soc. Perkin Transactions 1, 5, 483-487 (1978). Further, a pyrrole derivative having an aminocarbonyl group as a substituent is described as a therapeutic agent for an immune or allergic disease in WO 2005/123671. However, a pyrrole derivative having both ureido group and aminocarbonyl group as substituents is unknown, and a pyrrole derivative having also a bicyclic group in addition to these substituents is an entirely unknown compound, and as a matter of course, the use thereof is also not known.